The purpose of the study is to assess the effect of everolimus initiation together with reduction or discontinuation of calcineurin inhibitor (CNI) on renal function in maintenance liver transplant recipients with CNI-related renal impairment, while maintaining efficacy.

The composite efficacy failure endpoint encompasses at least one of: biopsy proven acute rejection, graft loss, or death for the patient. BPAR was defined as a clinically suspected acute rejection confirmed by biopsy. Acute rejection episodes were recorded as Liver Allograft Rejection. The allograft was presumed to be lost if a patient had a liver retransplant or died.

1.5 mg bid adjusted in order to achieve a trough level between 3 and 8 ng/mL while in combination with CNI and between 6 and 12 ng/mL after CNI discontinuation

Other Names:

Certican

RAD001

Neoral®/Prograf®

Drug: Calcineurin inhibitors (CNI)

Other Name: Neoral/Prograf

Drug: Steroids

Experimental: CNI continuation ± MPA/AZA ± Steroids

Standard CNI dose ± MPA/AZA ± steroids

Drug: Calcineurin inhibitors (CNI)

Other Name: Neoral/Prograf

Drug: Mycophenolate acid (MPA)/ Azathioprine (AZA)

Other Name: Myfortic/Cellecept

Drug: Steroids

Eligibility

Ages Eligible for Study:

18 Years to 70 Years (Adult, Senior)

Genders Eligible for Study:

Both

Criteria

Inclusion criteria

Male or female 18 - 70 years old

Patient who has undergone a primary liver transplantation 12 to 60 months ago from a cadaveric or a living donor

Patient with a calculated GFR ≤ 60 and ≥ 20mL/min

Patient receiving tacrolimus with C0-h level ≥ 3 and ≤ 8 ng/mL or Neoral® with C0-h level ≥ 50 and ≤ 150 ng/mL or with C2-h level ≥ 250 ng/mL and ≤ 650 ng/mL with or without any of the following (MPA or AZA or steroids)

Patient willing and capable of giving written informed consent for study participation and able to participate in the study for 6 months

Patient in whom an allograft biopsy will not be contraindicated

Female capable of becoming pregnant must have a negative pregnancy test prior to randomization and are required to practice a medically approved method of birth control for the duration of the study

Exclusion criteria

Recipient of multiple solid organ transplants

Patient on dialysis

Patient with an identifiable cause of renal dysfunction other than CNI toxicity

Patient with proteinuria ≥ 1.0 g/24h

Patient with any acute rejection within 6 months prior to randomization

Undergone a liver transplantation for a hepatocellular carcinoma with sign of recurrence;

Severe graft dysfunction;

HCV positive patient who needs an active anti-viral treatment

HIV positive patient

Patient who is breast feeding

Patient with a current severe systemic infection

Patient who has received an unlicensed drug or therapy within one month prior to study entry

Presence of any hypersensitivity to drugs similar to everolimus (e.g. macrolides)

Use of any other immunosuppressive drugs than tacrolimus/cyclosporine microemulsion, steroids, azathioprine and mycophenolic acid

Additional protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00267189